The purpose of the proposed research is to investigate protein-DNA interactions in human chromosomes in cells from healthy and diseased individuals. The structural organization, replication, stability and repair of human chromosomes will be studied by spectroscopic, biochemical, and cell biological techniques. Methods will be developed and utilized in attempts to understand genetic control, in particular X chromosome inactivation, and inherited conditions with increased susceptibility to neoplastic transformation. BIBLIOGRAPHIC REFERENCES: Brodie, S., Giron, J., and Latt, S.A.: Estimation of Accessibility of DNA in Chromatin from Fluorescence Measurements of Electronic Excitation Energy Transfer. Nature 253:470-471, 1975. Latt, S.A.: Fluorescence Analysis of late DNA Replication in Human Metaphase Chromosomes. Somatic Cell Genetics 1:293-307, 1975.